TY - JOUR
T1 - Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration – A transdiagnostic study cross-validating atrophy and fluid biomarkers
AU - FTLD Consortium Germany
AU - Hüper, Lea
AU - Steinacker, Petra
AU - Polyakova, Maryna
AU - Mueller, Karsten
AU - Godulla, Jannis
AU - Herzig, Sabine
AU - Danek, Adrian
AU - Engel, Annerose
AU - Diehl-Schmid, Janine
AU - Classen, Joseph
AU - Fassbender, Klaus
AU - Fliessbach, Klaus
AU - Jahn, Holger
AU - Kassubek, Jan
AU - Kornhuber, Johannes
AU - Landwehrmeyer, Bernhard
AU - Lauer, Martin
AU - Obrig, Hellmuth
AU - Oeckl, Patrick
AU - Prudlo, Johannes
AU - Saur, Dorothee
AU - Anderl-Straub, Sarah
AU - Synofzik, Matthis
AU - Wagner, Matias
AU - Wiltfang, Jens
AU - Winkelmann, Juliane
AU - Volk, Alexander E.
AU - Huppertz, Hans Jürgen
AU - Otto, Markus
AU - Schroeter, Matthias L.
N1 - Publisher Copyright:
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2024/7
Y1 - 2024/7
N2 - INTRODUCTION: Frontotemporal lobar degeneration (FTLD) encompasses behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy, corticobasal syndrome/degeneration, and primary progressive aphasias (PPAs). We cross-validated fluid biomarkers and neuroimaging. METHODS: Seven fluid biomarkers from cerebrospinal fluid and serum were related to atrophy in 428 participants including these FTLD subtypes, logopenic variant PPA (lvPPA), Alzheimer's disease (AD), and healthy subjects. Atrophy was assessed by structural magnetic resonance imaging and atlas-based volumetry. RESULTS: FTLD subtypes, lvPPA, and AD showed specific profiles for neurofilament light chain, phosphorylated heavy chain, tau, phospho-tau, amyloid beta1-42 from serum/cerebrospinal fluid, and brain atrophy. Neurofilaments related to regional atrophy in bvFTD, whereas progranulin was associated with atrophy in semantic variant PPA. Ubiquitin showed no effects. DISCUSSION: Results specify biomarker and atrophy patterns in FTLD and AD supporting differential diagnosis. They identify neurofilaments and progranulin in interaction with structural imaging as promising candidates for monitoring disease progression and therapy. Highlights: Study cross-validated neuroimaging and fluid biomarkers in dementia. Five kinds of frontotemporal lobar degeneration and two variants of Alzheimer's disease. Study identifies disease-specific fluid biomarker and atrophy profiles. Fluid biomarkers and atrophy interact in a disease-specific way. Neurofilaments and progranulin are proposed as biomarkers for diagnosis and therapy.
AB - INTRODUCTION: Frontotemporal lobar degeneration (FTLD) encompasses behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy, corticobasal syndrome/degeneration, and primary progressive aphasias (PPAs). We cross-validated fluid biomarkers and neuroimaging. METHODS: Seven fluid biomarkers from cerebrospinal fluid and serum were related to atrophy in 428 participants including these FTLD subtypes, logopenic variant PPA (lvPPA), Alzheimer's disease (AD), and healthy subjects. Atrophy was assessed by structural magnetic resonance imaging and atlas-based volumetry. RESULTS: FTLD subtypes, lvPPA, and AD showed specific profiles for neurofilament light chain, phosphorylated heavy chain, tau, phospho-tau, amyloid beta1-42 from serum/cerebrospinal fluid, and brain atrophy. Neurofilaments related to regional atrophy in bvFTD, whereas progranulin was associated with atrophy in semantic variant PPA. Ubiquitin showed no effects. DISCUSSION: Results specify biomarker and atrophy patterns in FTLD and AD supporting differential diagnosis. They identify neurofilaments and progranulin in interaction with structural imaging as promising candidates for monitoring disease progression and therapy. Highlights: Study cross-validated neuroimaging and fluid biomarkers in dementia. Five kinds of frontotemporal lobar degeneration and two variants of Alzheimer's disease. Study identifies disease-specific fluid biomarker and atrophy profiles. Fluid biomarkers and atrophy interact in a disease-specific way. Neurofilaments and progranulin are proposed as biomarkers for diagnosis and therapy.
KW - amyloid
KW - atrophy
KW - fluid biomarkers
KW - frontotemporal dementia
KW - frontotemporal lobar degeneration
KW - magnetic resonance imaging
KW - neurofilaments
KW - phospho-tau
KW - progranulin
KW - tau
KW - ubiquitin
UR - https://www.scopus.com/pages/publications/85195691969
U2 - 10.1002/alz.13863
DO - 10.1002/alz.13863
M3 - Article
AN - SCOPUS:85195691969
SN - 1552-5260
VL - 20
SP - 4461
EP - 4475
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 7
ER -